Over the past few decades, abnormalities in sensory functions, such as tactile, proprioceptive and nociceptive processing, have been increasingly recognized in patients with focal dystonias. In this ...Review, we ask whether sensory system abnormalities are specific to particular types of dystonia, whether a causal link exists between sensory alterations and dystonic motor activity and how mechanisms underlying the sensory abnormalities fit in with the proposed 'network model' of dystonia. We suggest that alterations in the various sensory modalities participate at three different levels in the pathophysiological cascade that leads to dystonia: a background level that predisposes individuals to dystonia, a disease-related level that is evident only when dystonia becomes manifest and a causative level that triggers dystonia. We conclude that it is crucial to study sensory as well as motor pathophysiology to fully understand focal dystonias.
Changes in sensory function that have been described in patients with Parkinson disease (PD) can be either 'pure' disorders of conscious perception such as elevations in sensory threshold, or ...disorders of sensorimotor integration, in which the interaction between sensory input and motor output is altered. In this article, we review the extensive evidence for disrupted tactile, nociceptive, thermal and proprioceptive sensations in PD, as well as the influences exerted on these sensations by dopaminergic therapy and deep brain stimulation. We argue that abnormal spatial and temporal processing of sensory information produces incorrect signals for the preparation and execution of voluntary movement. Sensory deficits are likely to be a consequence of the dopaminergic denervation of the basal ganglia that is the hallmark of PD. A possible mechanism to account for somatosensory deficits is one in which disease-related dopaminergic denervation leads to a loss of response specificity, resulting in transmission of noisier and less-differentiated information to cortical regions. Changes in pain perception might have a different explanation, possibly involving disease-related effects outside the basal ganglia, including involvement of peripheral pain receptors, as well as structures such as the periaqueductal grey matter and non-dopaminergic neurotransmitter systems.
Background and aims:
No consensus exists on how aggressively to treat relapsing–remitting multiple sclerosis (RRMS) nor on the timing of the treatment. The objective of this study was to evaluate ...disability trajectories in RRMS patients treated with an early intensive treatment (EIT) or with a moderate-efficacy treatment followed by escalation to higher-efficacy disease modifying therapy (ESC).
Methods:
RRMS patients with ⩾5-year follow-up and ⩾3 visits after disease modifying therapy (DMT) start were selected from the Italian MS Registry. EIT group included patients who received as first DMT fingolimod, natalizumab, mitoxantrone, alemtuzumab, ocrelizumab, cladribine. ESC group patients received the high efficacy DMT after ⩾1 year of glatiramer acetate, interferons, azathioprine, teriflunomide or dimethylfumarate treatment. Patients were 1:1 propensity score (PS) matched for characteristics at the first DMT. The disability trajectories were evaluated by applying a longitudinal model for repeated measures. The effect of early versus late start of high-efficacy DMT was assessed by the mean annual Expanded Disability Status Scale (EDSS) changes compared with baseline values (delta-EDSS) in EIT and ESC groups.
Results:
The study cohort included 2702 RRMS patients. The PS matching procedure produced 363 pairs, followed for a median (interquartile range) of 8.5 (6.5–11.7) years. Mean annual delta-EDSS values were all significantly (p < 0.02) higher in the ESC group compared with the EIT group. In particular, the mean delta-EDSS differences between the two groups tended to increase from 0.1 (0.01–0.19, p = 0.03) at 1 year to 0.30 (0.07–0.53, p = 0.009) at 5 years and to 0.67 (0.31–1.03, p = 0.0003) at 10 years.
Conclusion:
Our results indicate that EIT strategy is more effective than ESC strategy in controlling disability progression over time.
•Somatosensory temporal discrimination threshold (STDT) is abnormal in PD.•Prolonged STDT in PD correlates with the degree of nigrostriatal dopamine loss.•Prolonged STDT in PD generates incorrect ...signals for the execution and control of finger movements.
The somatosensory temporal discrimination threshold (STDT), defined as the shortest time interval required for two tactile stimuli to be perceived as separate, is longer in patients with Parkinson’s disease (PD). In this review, we discuss STDT findings in healthy subjects and in PD patients and the relationship between altered STDT and motor disturbances.
A search was conducted on PubMed for papers dealing with PD and temporal discrimination published from January 1990 to July 2017.
Abnormal STDT in PD correlates with disease duration, disease severity and degree of nigrostriatal dopamine loss, and responds to dopaminergic medication. In PD, a prolonged STDT does not correlate, or only marginally correlates, with clinically assessed bradykinesia of finger tapping. By contrast, a prolonged STDT correlates with the variability in amplitude and speed of finger tapping as assessed by means of neurophysiological techniques and may contribute to impaired finger dexterity in PD.
We suggest that abnormal temporal processing of sensory information in PD generates incorrect signals for the execution and control of voluntary movements.
This review sheds light on unsolved questions regarding the relationship between STDT alterations and motor disturbances in PD and proposes directions for future research on this topic.
Neural oscillations can be modulated by non-invasive brain stimulation techniques, including transcranial alternating current stimulation (tACS). However, direct evidence of tACS effects at the ...cortical level in humans is still limited. In a tACS-electroencephalography co-registration setup, we investigated the ability of tACS to modulate cortical somatosensory information processing as assessed by somatosensory-evoked potentials (SEPs). To better elucidate the neural substrates of possible tACS effects we also recorded peripheral and spinal SEPs components, high-frequency oscillations (HFOs), and long-latency reflexes (LLRs). Finally, we studied whether changes were limited to the stimulation period or persisted thereafter. SEPs, HFOs, and LLRs were recorded during tACS applied at individual mu and beta frequencies and at the theta frequency over the primary somatosensory cortex (S1). Sham-tACS was used as a control condition. In a separate experiment, we assessed the time course of mu-tACS effects by recording SEPs before (T0), during (T1), and 1 min (T2) and 10 min (T3) after stimulation. Mu-tACS increased the amplitude of the N20 component of SEPs compared to both sham and theta-tACS. No differences were found between sham, beta-, and theta-tACS conditions. Also, peripheral and spinal SEPs, P25, HFOs, and LLRs did not change during tACS. Finally, mu-tACS-induced modulation of N20 amplitude specifically occurred during stimulation (T1) and vanished afterwards (i.e., at T2 and T3). Our findings suggest that TACS applied at the individual mu frequency is able to modulate early somatosensory information processing at the S1 level and the effect is limited to the stimulation period.
Salivary caffeine in Parkinson's disease Leodori, Giorgio; De Bartolo, Maria Ilenia; Belvisi, Daniele ...
Scientific reports,
05/2021, Letnik:
11, Številka:
1
Journal Article
Recenzirano
Odprti dostop
We aimed to investigate salivary caffeine content, caffeine absorption and metabolism in Parkinson's disease (PD) and verify whether salivary caffeine can be used as a biomarker of PD. We enrolled 98 ...PD patients and 92 healthy subjects. Caffeine and its major metabolite, paraxanthine, were measured in saliva samples collected before and 4 h after the oral intake of caffeine (100 mg). We measured caffeine absorption as the normalized increase in caffeine levels, and caffeine metabolism as the paraxanthine/caffeine ratio. The Movement Disorder Society Unified Parkinson's Disease Rating Scale part III, the Hoehn & Yahr, the presence of motor complications, and levodopa equivalent dose (LED) were assessed and correlated with caffeine levels, absorption, and metabolism. The effects of demographic and environmental features possibly influencing caffeine levels were also investigated. Caffeine levels were decreased in patients with moderate/advanced PD, while caffeine levels were normal in patients with early and de-novo PD, unrelated to caffeine intake. Caffeine absorption and metabolism were normal in PD. Decreased salivary caffeine levels in PD were associated with higher disease severity, longer duration, and the presence of motor complications, no significant association was found with LED. Salivary caffeine decrease correlates with PD progression.
•Oromandibular dystonia (OMD) differs from other forms of focal idiopathic dystonia.•Masticatory and facial systems have some peculiar neuroanatomical and physiological features.•Abnormal processing ...of somatosensory inputs possibly plays a prominent role in the pathophysiology of OMD.
Oromandibular dystonia (OMD) is a rare form of focal idiopathic dystonia. OMD was clinically identified at the beginning of the 20th century, and the main clinical features have been progressively described over the years. However, OMD has several peculiarities that still remain unexplained, including the high rate of oral trauma, which is often related to the onset of motor symptoms. The purpose of this paper was to formulate a hypothesis regarding the pathophysiology of OMD, starting from the neuroanatomical basis of the masticatory and facial systems and highlighting the features that differentiate this condition from other forms of focal idiopathic dystonia. We provide a brief review of the clinical and etiological features of OMD as well as neurophysiological and neuroimaging findings obtained from studies in patients with OMD. We discuss possible pathophysiological mechanisms underlying OMD and suggest that abnormalities in sensory input processing may play a prominent role in OMD pathophysiology, possibly triggering a cascade of events that results in sensorimotor cortex network dysfunction. Finally, we identify open questions that future studies should address, including the effect of abnormal sensory input processing and oral trauma on the peculiar neurophysiological abnormalities observed in OMD.
Background:
We investigated the effectiveness and safety of mirabegron oral treatment in a group of patients with Parkinson’s disease (PD) and overactive bladder (OAB), refractory to antimuscarinics.
...Materials and methods:
Thirty patients with PD and refractory OAB were prospectively included in the study. At baseline, motor symptoms, severity of disease and cognitive status were assessed with the Hoehn–Yahr Scale, the Unified Parkinson’s disease Rating Scale, the Mini Mental State examination and the Montreal Cognitive Assessment. At baseline, urinary symptoms, satisfaction with treatment and the impact of urinary incontinence on quality of life (QoL) were assessed with the 3-day voiding diary, the Visual Analogue Scale (VAS), the Incontinence–QoL questionnaire and urodynamics. Patients started assuming mirabegron 50 mg tablets once daily. Evaluation of urinary symptoms and related questionnaires, motor symptoms, severity of PD and uroflowmetry with postvoid residual volume measurement were then repeated at the 3- and 6-month follow up. Side effects were also noted.
Results:
At baseline, the most frequently reported urinary symptoms were: urinary urgency (present in all the patients), urge urinary incontinence in 28/30 (93.3%) and increased daytime urinary frequency in 25 (83.3%) patients. At the 3-month follow up, 7 out of the 30 patients achieved a complete urinary continence. Significant improvements in VAS and Incontinence–QoL scores were observed in 24 patients. These benefits were maintained for the whole observation period. Four patients discontinued treatment due to poor efficacy, and two due to the cost of the drug.
Conclusions:
Mirabegron is a safe and effective treatment in patients with PD and OAB refractory to anticholinergics in the short-term follow up.
•MEP facilitation following intermittent theta-burst stimulation (iTBS) is associated with specific iTBS-evoked EEG oscillations.•Baseline MEP amplitude and iTBS-evoked beta oscillations predict iTBS ...aftereffects.•Our TMS-EEG study identified cortical mechanisms underlying iTBS variability that are potentially clinically relevant.
To test the hypothesis that intermittent theta burst stimulation (iTBS) variability depends on the ability to engage specific neurons in the primary motor cortex (M1).
In a sham-controlled interventional study on 31 healthy volunteers, we used concomitant transcranial magnetic stimulation (TMS) and electroencephalography (EEG). We compared baseline motor evoked potentials (MEPs), M1 iTBS-evoked EEG oscillations, and resting-state EEG (rsEEG) between subjects who did and did not show MEP facilitation following iTBS. We also investigated whether baseline MEP and iTBS-evoked EEG oscillations could explain inter and intraindividual variability in iTBS aftereffects.
The facilitation group had smaller baseline MEPs than the no-facilitation group and showed more iTBS-evoked EEG oscillation synchronization in the alpha and beta frequency bands. Resting-state EEG power was similar between groups and iTBS had a similar non-significant effect on rsEEG in both groups. Baseline MEP amplitude and beta iTBS-evoked EEG oscillation power explained both inter and intraindividual variability in MEP modulation following iTBS.
The results show that variability in iTBS-associated plasticity depends on baseline corticospinal excitability and on the ability of iTBS to engage M1 beta oscillations.
These observations can be used to optimize iTBS investigational and therapeutic applications.
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